The effects of dietary supplementation with rosemary oil (RO), Nigella sativa oil (NSO) and their combination (NSO+RO) were studied in Japanese quails challenged with Escherichia coli. Thirty hundred quail chicks were randomly allocated to 5 equal groups, each of 3 replicates (20 quails/ replicate). Quails in the negative and positive control groups were fed a basal diet based on maize and soybean with vegetable oil as a lipid source. The experimental dietary groups were fed basal diet with RO, NSO or NSO+RO as a lipid source. At day 33 of age, birds from all groups, except negative control, were injected subcutaneously with 200 μl of E. coli. It was shown that NSO and NSO+RO addition significantly improved final body weight and body weight gain in comparison with both control groups. Additionally, the supplementation with RO, NSO or their combination reduced serum liver and kidney functions biomarkers, decreased MDA level and increased antioxidant enzymes activity in both liver and breast muscle in comparison with the positive control. Moreover, serum lysozyme and bactericidal activities were significantly increased in all experimental dietary groups. Furthermore, NSO and NSO+RO treatments suppressed harmful bacteria like E. coli, increased coliforms and lactobacilli bacteria in comparison with the RO group, and also significantly alleviated histopathological and morphometric changes induced by E. coli in the small intestine, spleen and bursa of Fabricius. In conclusion, NSO and RO can exert antioxidant and immunomodulatory effects. However, NSO alone or combined with RO is more effective than RO as a growth promoter and for controlling intestinal pathogenic bacteria.